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2.
Transl Oncol ; 14(8): 101119, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34000643

RESUMO

Relapse of childhood AML1-ETO (AE) acute myeloid leukemia is the most common cause of treatment failure. Optimized minimal residual disease monitoring methods is required to prevent relapse. In this study, we used next-generation sequencing to identify the breakpoints in the fusion gene and the DNA-based droplet digital PCR (ddPCR) method was used for dynamic monitoring of AE-DNA. The ddPCR technique provides more sensitive and precise quantitation of the AE gene during disease progression and relapse. Quantification of the AE fusion gene by ddPCR further contributes to improved prognosis. Our study provides valuable methods for dynamic surveillance of AE fusion DNA and assistance in determining the prognosis.

3.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657410

RESUMO

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Assuntos
COVID-19/imunologia , Megacariócitos/imunologia , Monócitos/imunologia , RNA Viral , SARS-CoV-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/isolamento & purificação , Análise de Célula Única , Transcriptoma/imunologia , Adulto Jovem
4.
Sci China Life Sci ; 64(10): 1634-1644, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33564978

RESUMO

The blood and immune system of coronavirus disease 2019 (COVID-19) infected patients are dysfunctional, and numerous studies have been conducted to resolve their characteristics and pathogenic mechanisms. Nevertheless, the variations of immune responses along with disease severity have not been comprehensively documented. Here, we profiled the single-cell transcriptomes of 96,313 peripheral blood mononuclear cells (PBMCs) derived from 12 COVID-19 patients (including four moderate, four severe and four critical cases) and three healthy donors. We showed that proliferative CD8 effector T cells with declined immune functions and cytotoxicity accumulated in the critical stage. By contrast, the quantity of natural killer (NK) cells was significantly reduced, while they exhibited enhanced immune activities. Notably, a gradually attenuated responseto COVID-19 along with disease severity was observed in monocytes, in terms of cellular composition, transcriptional discrepancy and transcription factor regulatory network. Furthermore, we identified immune cell-type dependent cytokine signatures distinguishing the severity of COVID-19 patients. In addition, cell interactions between CD8 effector T/NK cells and monocytes mediated by inflammatory cytokines were enhanced in moderate and severe stages, but weakened in critical cases. Collectively, our work uncovers the cellular and molecular players underlying the disordered and heterogeneous immune responses associated with COVID-19 severity, which could provide valuable insights for the treatment of critical COVID-19 patients.


Assuntos
COVID-19/fisiopatologia , Leucócitos Mononucleares/metabolismo , Índice de Gravidade de Doença , Análise de Célula Única , Transcriptoma , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/sangue , COVID-19/genética , COVID-19/virologia , Estudos de Casos e Controles , Humanos , Células Matadoras Naturais/imunologia , SARS-CoV-2/isolamento & purificação
5.
J Pharm Biomed Anal ; 210: 114560, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34999436

RESUMO

A simple and non-invasive detection method for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) was established by systematically investigating the characteristics of bone marrow supernatants from 61 AML patients, 22 ALL patients, and 5 volunteers without hematological tumors by Raman spectroscopy and orthogonal partial least squares discriminant analysis (OPLS-DA). The control group could be well distinguished from the AML and ALL groups by Raman peaks of 859, 1031, 1437, 1443, 1446, 1579, and 1603 cm-1 and from the AML subtypes groups (AML-M2, AML-M3, AML-M4, and AML-M5) by the Raman peaks of 859, 1221, 1230, 1437, 1443, and 1603 cm-1, indicating high sensitivity and specificity of the method. Potentially important variables of acute leukemia (AL) prognosis, such as cholesterol, high-density lipoprotein, low-density lipoprotein, adenosine deaminase, and hemoglobin, could be effectively identified by Raman peaks of 1437, 1443, and 1579 cm-1. Therefore, Raman spectroscopy can be considered as a new non-invasive clinical tool for the detection of different types of AL and can be used to correlate biochemical parameters of AL patients with the classification and prognosis of AL.

6.
Oncogene ; 39(50): 7239-7252, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33037410

RESUMO

Epigenetic regulations play crucial roles in leukemogenesis and leukemia progression. SUV39H1 is the dominant H3K9 methyltransferase in the hematopoietic system, and its expression declines with aging. However, the role of SUV39H1 via its-mediated repressive modification H3K9me3 in leukemogenesis/leukemia progression remains to be explored. We found that SUV39H1 was down-regulated in a variety of leukemias, including MLL-r AML, as compared with normal individuals. Decreased levels of Suv39h1 expression and genomic H3K9me3 occupancy were observed in LSCs from MLL-r-induced AML mouse models in comparison with that of hematopoietic stem/progenitor cells. Suv39h1 overexpression increased leukemia latency and decreased the frequency of LSCs in MLL-r AML mouse models, while Suv39h1 knockdown accelerated disease progression with increased number of LSCs. Increased Suv39h1 expression led to the inactivation of Hoxb13 and Six1, as well as reversion of Hoxa9/Meis1 downstream target genes, which in turn decelerated leukemia progression. Interestingly, Hoxb13 expression is up-regulated in MLL-AF9-induced AML cells, while knockdown of Hoxb13 in MLL-AF9 leukemic cells significantly prolonged the survival of leukemic mice with reduced LSC frequencies. Our data revealed that SUV39H1 functions as a tumor suppressor in MLL-AF9-induced AML progression. These findings provide the direct link of SUV39H1 to AML development and progression.


Assuntos
Progressão da Doença , Leucemia Mieloide Aguda/patologia , Metiltransferases/metabolismo , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Repressoras/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Feminino , Regulação Neoplásica da Expressão Gênica , Células-Tronco Hematopoéticas/citologia , Histonas/metabolismo , Humanos , Leucemia Mieloide Aguda/genética , Lisina/metabolismo , Metilação , Camundongos , Transcrição Genética
7.
Nat Prod Bioprospect ; 9(6): 425-429, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31724098

RESUMO

Two hitherto unknown iboga-type indole alkaloids, namely (3R)-7,19-di-epi-3-methoxytabernoxidine (1) and (3R,19R)-19-hydroxy-3-(2-oxopropyl)voacangine (2), together with eight known alkaloids (3-10), were isolated from the twigs and leaves of Tabernaemontana divaricata. Their structures were established on the basis of spectroscopic data interpretation, single crystal X-ray diffraction analysis and circular dichroism spectrum.

8.
Cancer Sci ; 110(7): 2200-2210, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31050834

RESUMO

Molecular genetic changes in acute myeloid leukemia (AML) play crucial roles in leukemogenesis, including recurrent chromosome translocations, epigenetic/spliceosome mutations and transcription factor aberrations. Six1, a transcription factor of the Sine oculis homeobox (Six) family, has been shown to transform normal hematopoietic progenitors into leukemia in cooperation with Eya. However, the specific role and the underlying mechanism of Six1 in leukemia maintenance remain unexplored. Here, we showed increased expression of SIX1 in AML patients and murine leukemia stem cells (c-Kit+ cells, LSCs). Importantly, we also observed that a higher level of Six1 in human patients predicts a worse prognosis. Notably, knockdown of Six1 significantly prolonged the survival of MLL-AF9-induced AML mice with reduced peripheral infiltration and tumor burden. AML cells from Six1-knockdown (KD) mice displayed a significantly decreased number and function of LSC, as assessed by the immunophenotype, colony-forming ability and limiting dilution assay. Further analysis revealed the augmented apoptosis of LSC and decreased expression of glycolytic genes in Six1 KD mice. Overall, our data showed that Six1 is essential for the progression of MLL-AF9-induced AML via maintaining the pool of LSC.


Assuntos
Proteínas de Homeodomínio/metabolismo , Leucemia Mieloide Aguda/patologia , Proteína de Leucina Linfoide-Mieloide/genética , Células-Tronco Neoplásicas/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Regulação para Cima , Animais , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Camundongos , Neoplasias Experimentais , Células-Tronco Neoplásicas/metabolismo , Prognóstico
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 1-7, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397810

RESUMO

OBJECTIVE: To investigate the Raman spectral characteristics of leukemia cells from 4 patients with acute promyelocytic leukemia (M3) and 3 patients with acute monoblastic leukemia (M5), establish a novel Raman label-free method to distinguish 2 kinds of acute myeloid leukemia cells so as to provide basis for clinical research. METHODS: Leukemia cells were collected from bone marrow of above-mentioned patients. Raman spectra were acquired by Horiba Xplora Raman spectrometer and Raman spectra of 30-50 cells from each patient were recorded. The diagnostic model was established according to principle component analysis (PCA), discriminant function analysis (DFA) and cluster analysis, and the spectra of leukemia cells from 7 patients were analyzed and classified. Characteristics of Raman spectra were analyzed combining with ultrastructure of leukemia cells. RESULTS: There were significant differences between Raman spectra of 2 kinds of leukemia cells. Compared with acute monoblastic leukemia cells, the spectra of acute promyelocytic leukemia cells showed stronger peaks in 622, 643, 757, 852, 1003, 1033, 1117, 1157, 1173, 1208, 1340, 1551, 1581 cm-1. The diagnostic models established by PCA-DFA and cluster analysis could successfully classify these Raman spectra of different samples with a high accuracy of 100% (233/233). The model was evaluated by "Leave-one-out" cross-validation and reached a high accuracy of 97% (226/233). CONCLUSION: The level of macromolecules of M3 cells is higher than that of M5. The diagnostic models established by PCA-DFA can classify these Raman spectra of different cells with a high accuracy. Raman spectra shows consistent result with ultrastructure by TEM.


Assuntos
Leucemia Mieloide Aguda , Análise por Conglomerados , Humanos , Leucemia Monocítica Aguda , Análise de Componente Principal , Análise Espectral Raman
10.
Toxicol Lett ; 268: 17-25, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28099878

RESUMO

Cardiotoxicity is one of the most serious side effects of new drugs. Early detection of the drug induced cardiotoxicity based on the biomarkers provides an important preventative strategy for detecting potential cardiotoxicity of candidate drugs. In this study, we aim to identify the predictive genomics biomarkers for drug-induced cardiac toxicity based on the RTCA coupled with PCR Array technology in primary cells. Three prototypical cardiotoxic compounds (doxorubicin, isoproterenol, ouabain) with different mechanisms were firstly real-time monitored to diagnose the cytotoxicity by using the RTCA, while the functional alterations of cardiomyocytes were also monitored by analyzing the beating frequency of cardiomyocytes. Then cardiac specific toxicity gene expression changes were studied by using the technology of PCR Array, which can detect the changes of 84 cardiac functions related genes. Rps6kb1 was identified to be the common cardiac biomarkers by using multivariate statistical and integration analyses. The biomarker was further verified by selecting other drugs with or without cardiotoxicity, and the results showed that the gene exhibited specific changes in cardiac toxicity. Moreover, IPA was applied to combine relevant pathways of Rps6kb1, and identify the main types of cardiac toxicity. These results would further enrich the evaluating strategy of drug-induced cardiotoxicity in vitro, and Rps6kb1 could be used as the specific biomarker of cardiotoxcity during safety assessment of the novel drug candidates.


Assuntos
Doxorrubicina/toxicidade , Perfilação da Expressão Gênica/métodos , Cardiopatias/induzido quimicamente , Cardiopatias/genética , Isoproterenol/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Ouabaína/toxicidade , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testes de Toxicidade , Animais , Animais Recém-Nascidos , Cardiotoxicidade , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Marcadores Genéticos , Cardiopatias/metabolismo , Cardiopatias/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
11.
Microbiol Res ; 192: 292-299, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27664748

RESUMO

5-Aminolevulinic acid (ALA), the committed intermediate of the heme biosynthetic pathway, attracts close attention among researchers because of its potential applications to cancer treatment and agriculture. Overexpression of heterologous hemA and hemL, which encode glutamyl-tRNA reductase and glutamate-1-semialdehyde aminotransferase, respectively, in Corynebacterium glutamicum produces ALA, although whether ALA accumulation causes unintended effects on the host is unknown. Here we used an integrated systems approach to compare global transcriptional changes induced by the expression of hemA and hemL. Metabolic pathway such as glycolysis was inhibited, but tricarboxylic acid cycle, pentose phosphate pathway, and respiratory metabolism were stimulated. Moreover, the transcriptional levels of certain genes involved in heme biosynthesis were up-regulated, and the data implicate the two-component system (TCS) HrrSA was involved in the regulation of heme synthesis. With these understandings, it is proposed that ALA accumulation stimulates heme synthesis pathway and respiratory metabolism. Our study illuminates the physiological effects of overexpressing hemA and hemL on the phenotype of C. glutamicum and contributes important insights into the regulatory mechanisms of the heme biosynthetic pathways.


Assuntos
Ácido Aminolevulínico/metabolismo , Corynebacterium glutamicum/fisiologia , Regulação Bacteriana da Expressão Gênica , Transcriptoma , Perfilação da Expressão Gênica , Glucose/metabolismo , Heme/biossíntese , Redes e Vias Metabólicas
12.
PLoS One ; 11(3): e0149586, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26930650

RESUMO

Aplastic anemia (AA) is a bone marrow failure syndrome that is caused largely by profound quantitative and qualitative defects of hematopoietic stem and progenitor cells. However, the mechanisms underlying these defects remain unclear. Under conditions of stress, autophagy acts as a protective mechanism for cells. We therefore postulated that autophagy in CD34+ hematopoietic progenitor cells (HPCs) from AA patients might be impaired and play a role in the pathogenesis of AA. To test this hypothesis, we tested autophagy in CD34+ cells from AA samples and healthy controls and investigated the effect of autophagy on the survival of adult human bone marrow CD34+ cells. We found that the level of autophagy in CD34+ cells from AA patients was significantly lower than in age/sex-matched healthy controls, and lower in cases of severe AA than in those with non-severe AA. Autophagy in CD34+ cells improved upon amelioration of AA but, compared to healthy controls, was still significantly reduced even in AA patients who had achieved a complete, long-term response. We also showed that although the basal autophagy in CD34+ cells was low, the autophagic response of CD34+ cells to "adversity" was rapid. Finally, impaired autophagy resulted in reduced differentiation and proliferation of CD34+ cells and sensitized them to death and apoptosis. Thus, our results confirm that autophagy in CD34+ cells from AA patients is impaired, that autophagy is required for the survival of CD34+ cells, and that impaired autophagy in CD34+ HPCs may play an important role in the pathogenesis of AA.


Assuntos
Anemia Aplástica/patologia , Antígenos CD34/análise , Autofagia , Células da Medula Óssea/patologia , Adulto , Células da Medula Óssea/citologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Appl Environ Microbiol ; 82(9): 2709-2717, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26921424

RESUMO

UNLABELLED: 5-Aminolevulinic acid (ALA), a nonprotein amino acid involved in tetrapyrrole synthesis, has been widely applied in agriculture, medicine, and food production. Many engineered metabolic pathways have been constructed; however, the production yields are still low. In this study, several 5-aminolevulinic acid synthases (ALASs) from different sources were evaluated and compared with respect to their ALA production capacities in an engineered Corynebacterium glutamicum CgS1 strain that can accumulate succinyl-coenzyme A (CoA). A codon-optimized ALAS from Rhodobacter capsulatus SB1003 displayed the best potential. Recombinant strain CgS1/pEC-SB produced 7.6 g/liter ALA using a mineral salt medium in a fed-batch fermentation mode. Employing two-stage fermentation, 12.46 g/liter ALA was produced within 17 h, with a productivity of 0.73 g/liter/h, in recombinant C. glutamicum Through overexpression of the heterologous nonspecific ALA exporter RhtA from Escherichia coli, the titer was further increased to 14.7 g/liter. This indicated that strain CgS1/pEC-SB-rhtA holds attractive industrial application potential for the future. IMPORTANCE: In this study, a two-stage fermentation strategy was used for production of the value-added nonprotein amino acid 5-aminolevulinic acid from glucose and glycine in a generally recognized as safe (GRAS) host,Corynebacterium glutamicum The ALA titer represented the highest in the literature, to our knowledge. This high production capacity, combined with the potential easy downstream processes, made the recombinant strain an attractive candidate for industrial use in the future.


Assuntos
Ácido Aminolevulínico/metabolismo , Corynebacterium glutamicum/metabolismo , Acil Coenzima A/biossíntese , Aminoácidos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas de Cultura Celular por Lotes/métodos , Vias Biossintéticas , Corynebacterium glutamicum/enzimologia , Corynebacterium glutamicum/genética , Escherichia coli/genética , Fermentação , Microbiologia Industrial/métodos , Engenharia Metabólica/métodos
14.
Appl Microbiol Biotechnol ; 99(6): 2593-602, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25586585

RESUMO

The copolymer poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] has the potential to serve as a biodegradable tissue engineering material. However, the production of this kind of copolymer still suffers from high cost and uncertainty. We describe here the design of metabolic pathways to synthesize P(HB-co-HHx) directly from glucose using recombinant Escherichia coli. By combining the BktB-dependent condensation pathway with the inverted ß-oxidation cycle pathway, we were able to synthesize a P(HB-co-HHx) copolymer with a 10 mol% HHx fraction in recombinant E. coli. After optimizing the host strain and employing thioesterase mutant strains, the engineered E. coli produced 12.9 wt% P(HB-co-HHx) with a 13.2 mol% 3HHx fraction.


Assuntos
Ácido 3-Hidroxibutírico/biossíntese , Escherichia coli/genética , Glucose/metabolismo , Engenharia Metabólica , Vias Biossintéticas , Caproatos , Meios de Cultura , Primers do DNA , DNA Bacteriano/genética , Escherichia coli/metabolismo , Plasmídeos/genética
15.
Nanotoxicology ; 8(6): 686-96, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23837638

RESUMO

The aim of this work was to probe the biodistribution and toxic effects of silver nanoparticles (NPs) with powerful anti-bacterial and anti-virus activities. For this purpose, novel silver NPs with gold nanorod (NR) core and silver shell (Au@Ag NRs) were developed and employed as a model material. The inner gold core provided an excellent internal reference for tracking the NRs in vivo. After subcutaneous injection of Au@Ag NRs, silver and gold contents in the subcutis and organs were examined by inductively coupled plasma mass spectrometry at different time points within 28 days. Histological analysis, physiological function and complement faction 3 (C3) and 5a (C5a) measurement were performed over time to reveal the toxic effect of Au@Ag NRs in vivo. Experimental results showed that majority of the Au@Ag NRs remained in the injection site except for a small amount migrating into the lymph nodes. The silver shell was dissolved in the subcutaneous tissue and released silver ions rapidly, which resulted in detectable silver accumulation in most of the organs. The accumulated silver ions in the kidney not only interacted with the kidney cells membrane but also induced a rapid increase of complement fraction C3 followed by a significant consumption and C3a and C5a production significantly in the serum, which resulted in kidney oxidative damage and eventually led to the morphological changes and filtration function impairment of the glomerulus. The released silver ions also caused oxidative injury of subcutaneous tissue in the injection site.


Assuntos
Ouro/farmacocinética , Ouro/toxicidade , Nanotubos/toxicidade , Prata/farmacocinética , Prata/toxicidade , Animais , Feminino , Ouro/administração & dosagem , Ouro/química , Injeções Subcutâneas , Rim/efeitos dos fármacos , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanotubos/química , Prata/administração & dosagem , Prata/química , Distribuição Tecidual
16.
J Nanosci Nanotechnol ; 13(2): 1467-71, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23646662

RESUMO

Biocompatibility has been one of the most crucial performances that determine the clinical application potentials of biomaterials and implants. As carbon is one inner substance and possesses clinical accepted blood compatibility, carbon nanotubes may bring improved hemocompatibility of polymeric materials when used as fillers. In this work, a kind of composite composed of polyurethane and multiwalled carbon nanotubes has been developed using a customized sol-gel technique. The cytotoxicity of the composite was evaluated by examining viability of the endothelium cells seeded on the composite or cultured with composite extraction using MTS assay and Environmental Scanning Electronic Microscope. Tissue compatibility was evaluated by subcutaneous implantation of the composite film in the paraspinal skin incision of rat. Dynamic clotting test of the composite were conducted to evaluate blood compatibility. Experiments results revealed that multiwalled carbon nanotubes were well dispersed into the polyurethane matrix. More functional endothelial cell grew on the composite than polyurethane. When implanted subcutaneously, the composite did not induce long-term inflammation in the implanted sites and exhibited good tissue compatibility. The dynamic clotting test showed that the composite had longer clotting time than PU, indicating that anti-coagulant property of the composite was improved.


Assuntos
Materiais Biocompatíveis , Nanotubos de Carbono , Poliuretanos/química , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar
17.
PLoS One ; 7(7): e38995, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22808023

RESUMO

In this work the effects of four different multiwalled carbon nanotubes (MWCNTs), including long carboxylated (L-COOH), short carboxylated (S-COOH), long aminated (L-NH(2)) and short aminated (S-NH(2)) ones, on the integrity of red blood cells, coagulation kinetics and activation of platelets were investigated with human whole blood. We found that the four MWCNTs induced different degrees of red blood cell damage as well as a mild level of platelet activation (10-25%). L-COOH and L-NH(2) induced a higher level of platelet activation than S-COOH and S-NH(2) respectively; meanwhile L-NH(2) caused marked reductions in platelet viability. The presence of the four MWCNTs led to earlier fibrin formation, L-NH(2) increased the clots hardness significantly, while L-COOH and S-NH(2) made the clots become softer. It was concluded that the four MWCNTs affected blood coagulation process and the clots mechanical properties; they also altered the integrity of the red blood cells and the viability of the platelets, as well as induced platelets activation. The effects of MWCNTs depended on the size and chemistry of the nanotubes and the type of cells they contacted.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Aminação , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Ácidos Carboxílicos/química , Sobrevivência Celular/efeitos dos fármacos , Diaminas/química , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Fibrina/química , Hemólise/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Varredura , Ativação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas
18.
Theranostics ; 2(3): 258-70, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22509194

RESUMO

Macrophages are one of the most important types of immune effector cells and are closely associated with tumor progression and metastasis. In this work, we investigated the influences of oxidized multiwalled carbon nanotubes (o-MWCNT) on macrophages that are resting in the normal subcutis tissue or in the tumor microenvironment in vivo as well as on the macrophage cell line of RAW 264.7 treated with combination of IL4, IL10 and IL13 in vitro. The o-MWCNT were characterized with SEM, DLS, FTIR, TGA, and UV-vis-NIR spectroscopy, and their effects on the RWA 264.7 cell line and breast cancer tumor-bearing mice were analyzed using the MTS assay, flow cytometry analysis, and histological and immunohistochemical observations. Our experimental results showed that subcutaneously injected o-MWCNT not only induced phagocytosis of the local resident macrophages, but also competitively recruited macrophages from other tissues. These interactions resulted in macrophage reduction and decreased vessel density around the tumor mass, which together inhibited tumor progression and metastasis in the lung. In the cell line model, the o-MWCNT inhibited the ability of the interleukin treated RAW macrophages to promote tumor cell migration as well as decreased their proliferation rate.

19.
J Nanosci Nanotechnol ; 10(11): 7550-3, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21137980

RESUMO

Interaction of nanomaterials to protein molecules is one of the most important issues to deeply understand the influences of the nanomaterials upon physiological processes and protein functions. So far most of investigations focused on the protein molecules adsorbed on the nanomaterials surface, less is known about those in the aqueous phase (not absorbed). In this work, luminescent spectroscopy analysis, circular dichroism measurement, atomic force microscopy, matrix-assisted laser desorption/ionization time of flight mass spectrometry, isoelectric focusing and sulfate polyacrylamide gel electrophoresis were used to investigate the influence of oxidized water-soluble multiwalled carbon nanotubes (CNT) dispersing in aqueous solution upon the structures of bovine serum albumin (BSA) through co-incubation. We focused on BSA molecules that stayed in the aqueous phase instead of those adsorbed by CNT. Experimental results show that the fractions of beta-sheet decreased from 33.3% to 29.8% and beta-turn increased from 2% to 5% in reference with native BSA. There was a slight increase of alpha-helix and a slight reduction of random coil. BSA molecules that had been encountered with CNT and were left in the solution formed a loose and flatten morphology on graphite substrates instead of their native tight and round morphology observed by AFM. The value of isoelectric point for BSA after exposed to CNT moved towards to a higher pH position compared with native BSA. All together, it was concluded that the oxidized water-soluble multiwalled carbon nanotubes not only adsorb bovine serum albumin molecules to their surface, but also induces albumin molecules in the aqueous solution undergo secondary structure changes, which lead to a conformation change.


Assuntos
Nanotubos de Carbono , Soroalbumina Bovina/química , Adsorção , Dicroísmo Circular , Eletroforese em Gel de Poliacrilamida , Microscopia de Força Atômica , Peso Molecular , Estrutura Secundária de Proteína , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Água
20.
Bull Environ Contam Toxicol ; 84(4): 373-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20213192

RESUMO

In 2008, a total of 37 condoms was sampled from the Chinese market. Released nitrosamines and nitrosatable substances from the samples were monitored according to EN12868 method. Furthermore, to simulate the process of nitrosamines migration from condoms, a new and proper migration experiment was proposed in this study. N-nitrosodimethylamine, N-nitrosodiethylamine and N-nitrodibutylamine were found in almost all samples. The release levels of nitrosamines varied from 15.62 to 792.89 microg/kg. The proposed method is feasible, sensitive and accurate.


Assuntos
Preservativos , Nitrosaminas/análise , Técnicas de Química Analítica , China , Feminino , Humanos , Látex/análise , Masculino , Vagina/química
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